Early ART Can Restore Immune Systems of HIV-Positive Infants

A recent study found antiretroviral therapy (ART) conducted on infants born with HIV can successfully restore and reconstruct their immune systems.

The study found that by initiating ART early on, immune systems could preserve an expansion of naive T-cells, which allows for immune systems to return to a “normal” state.

With frequently missing data on HIV-positive infants, it makes it difficult for researchers to conduct immunological studies. Although blood samples are routinely taken to monitor their health and responses to treatment, it is hard to collect large volumes of blood for studies.

Furthermore, infants can miss visits because of caregivers who are unable to get them to a central location where samples are taken.

"Despite the best efforts of pediatricians and pediatric nurses, insufficient samples and missed visits have been the norm for pediatric studies in developing countries," said researcher Luis J. Montaner, DVM. "Loss of data lead to loss of statistical power, so it's extremely important to develop methods that allow us to analyze data sets where data are randomly missing."

In order to overcome missing data for these patients, researchers took 2 approaches: the Multiple Imputation method, which uses observed values and different imputation to fill in the gaps and make sure no other changes are made to the data. They also used the Bayesian model to create 5000 alternatives of the dataset, based on observed data.

These methods would be used to fix previous methods that have intrinsic issues, such as being unable to anticipate change over time and artificially reducing standard error.

The study took 66 HIV positive or seronegative infants born from HIV-infected mothers. They enrolled these patients into a trial called Children with HIV Early Antiretroviral Therapy (CHER). Every 6 months blood samples were taken and the patients received randomized ART either as soon as they were enrolled in the trial or when their CD4+T-cell count dropped below 20%.

The results of the study, published in PLOS ONE, showed that infants born with HIV can experience immunodefiency that could potentially lead to death or immune cell levels that are permanently offset when they do not receive ART. Researchers also found the infants had low levels of naïve CD4+ T-cells and other immune effectors.

By using the statistical methods, researchers found that early ART treatment results in higher CD4+ T-cell frequency, lower cellular activation, and higher proportions of naïve T-cells.

"Our study offers a field-based proof of concept that certain type of data missingness can be tolerated without affecting the integrity of a study," Montaner said. "We hope this will encourage other scientists to target hard-to-reach populations, particularly in resource-constrained settings."